Biopsy–Resection Concordance of CLDN18.2 Expression in Gastric Adenocarcinoma: Implications for Biomarker Interpretation in the Era of Targeted Therapy

Claudin 18.2 (CLDN18.2) is an emerging therapeutic biomarker in gastric adenocarcinoma. This study evaluated the concordance of CLDN18.2 expression between pretreatment biopsies and corresponding resection specimens and explored its associations with clinicopathological features and survival outcomes. This retrospective single-center study included 71 patients, 58 of whom received neoadjuvant chemotherapy. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. Concordance was assessed using Cohen’s kappa, positive percent agreement (PPA), negative percent agreement (NPA), and intraclass correlation coefficient (ICC). CLDN18.2 positivity was identified in 26.8% of biopsies and 21.1% of resection specimens. Categorical status was concordant in 65 of 71 patients (91.5%; κ = 0.769; p < 0.001), with a PPA of 73.7% and an NPA of 98.1%. Continuous analysis showed a high ICC (0.817; 95% confidence interval (CI), 0.722–0.881; p < 0.001). Six patients had discordant categorical results, all of whom had received neoadjuvant therapy. Exploratory survival analyses did not identify a statistically significant association between pretreatment biopsy CLDN18.2 status and overall survival (OS) or recurrence-free survival (RFS); however, the limited sample size and statistical precision preclude definitive conclusions regarding its prognostic significance. Overall, CLDN18.2 showed substantial biopsy–resection concordance, although positive agreement was lower than negative agreement. Discordant findings should be interpreted cautiously because treatment-related effects cannot be distinguished from spatial heterogeneity and sampling variation.